The present invention is in the area of organic synthesis and, in particular, methods of synthesizing high purity anhydride copolymers.
Aromatic polyanhydrides were first synthesized in 1909 by Bucher and Slade, as reported in J. Am. Chem. Soc. 31, 1319 (1909). Aliphatic polyanhydrides were first prepared in 1932 by Hill and Carothers, as described in J. Am. Chem. Soc. 54, 1569 (1932) and 55, 5023 (1933). A number of aromatic and heterocyclic polyanhydrides, intended as substitutes for polyesters in textile applications, were further investigated over the next thirty years.
Only a few papers have been published on the preparation of anhydride copolymers. In these studies anhydride copolymers were produced by mixing a calculated amount of two diacids, e.g., aromatic and aliphatic diacids, and treating with acetic anhydride to yield the mixed prepolymer. The mixed prepolymer was then polymerized by heating under vacuum. The reaction is shown in equation 1. The mixed prepolymer was not isolated nor purified prior to polymerization. ##STR1##
Using this method of preparation, N. Yoda et al. prepared anhydride copolymers composed of terephthalic acid, sebacic acid, adipic acid and five membered heterocyclic diacids, as described in Makromol. Chem. 56, 32 (1962), and Bull. Chem. Soc. Japan 1120 (1959) 32, Another anhydride copolymer composed of methylene bis(p-carboxyphenyl)amide and adipic acid was reported by N. Yoda in Chem. High Polymers Japan 19, 613 (1962). Unpurified mixed prepolymers were used in all these studies.
In a recent study by Leong et al., reported in J. Biomed Mat. Res., 19, 941 (1985), anhydride copolymers composed of bis(p-carboxyphenoxy)propane and sebacic acid were prepared. The copolymers were prepared from the mixed prepolymers obtained when the calculated amount of CPP and sebacic acid were treated with acetic anhydride. The mixed prepolymer was isolated after several weeks of crystallization at -20.degree. C. The composition of the final polymer was not controlled. Polymerization of the mixed prepolymers yielded polymers with molecular weights of 12,030. Unsuccessful attempts were made to obtain the copolymers by polycondensing the mixture of individually prepared prepolymers, especially sebacic acid prepolymers.
It is therefore an object of the present invention to provide a method for preparation of highly pure anhydride copolymers having a controlled composition, especially for use in biomedical applications.
It is a further object of the present invention to provide a method for preparation of highly pure anhydride copolymers with controlled composition which is reproducible, has a high yield and is quick.
It is a still further object of the present invention to provide a method for preparation of highly pure anhydride copolymers wherein prepolymers of the diacids are produced which can be combined to yield a wide variety of copolymers having an actual composition which is close to the calculated composition.
It is another object of the invention to provide a method for preparation of highly pure anhydride copolymers for use in preparing high molecular weight polyanhydrides.